Discovery of Dimeric Arylsulfonamides as Potent ADAM8 Inhibitors.

The metalloproteinase ADAM8 is upregulated in several cancers but has a dispensable function under physiological conditions. In tumor cells, ADAM8 is involved in invasion, migration, and angiogenesis. The use of bivalent inhibitors could impair migration and invasion through the double binding to a homodimeric form of ADAM8 located on the cell surface of tumor cells.

High b-value diffusion tractography: Abnormal axonal network organization associated with medication-refractory epilepsy.

Diffusion magnetic resonance imaging (dMRI) tractography has played a critical role in characterizing patterns of aberrant brain network reorganization among patients with epilepsy. However, the accuracy of dMRI tractography is hampered by the complex biophysical properties of white matter tissue. High b-value diffusion imaging overcomes this limitation by better isolating axonal pathways.

Cortical disconnection in temporal lobe epilepsy.

A critical concept in neurology is cortical disconnection, in which seemingly normal gray matter can have reduced function due to loss of white matter (WM) connections. White matter damage has been extensively described in temporal lobe epilepsy (TLE), but the anatomical distribution of cortical disconnection in TLE is not fully characterized. Here, we studied 221 participants (64 left-TLE, 55 right-TLE, 102 controls) from three different epilepsy treatment centers.

Patterns of seizure spread in temporal lobe epilepsy are associated with distinct white matter tracts.

Objective: It is commonly hypothesized that seizure spread patterns in patients with focal epilepsy are associated with structural brain pathways. However, this relationship is poorly understood and has not been fully demonstrated in patients with temporal lobe epilepsy. Here, we sought to determine whether directionality of seizure spread (DSS) is associated with specific cerebral white matter tracts in patients with temporal lobe epilepsy.

PedsQL™ Cognitive Functioning Scale in youth with epilepsy: Reliability and validity.

Objective: The objective of the study was to report on the internal consistency reliability and discriminant, concurrent and construct validity of the Pediatric Quality of Life Inventory™ (PedsQL™) Cognitive Functioning Scale as a brief generic cognitive functioning measure in youth with epilepsy.

Methods: The 6-item PedsQL™ Cognitive Functioning Scale and 23-item PedsQL™ 4.0 Generic Core Scales were completed by 221 pediatric patients ages 5-18 years with epilepsy and 336 parents of patients ages 2-18 years in a national field test study for the PedsQL™ Epilepsy Module.

Vulnerabilities to antiepileptic drug (AED) side effects in youth with epilepsy.

Objective: The objective of the study was to investigate the relationship between sociodemographic, seizure-related, behavioral health, and antiepileptic drug (AED) adverse effect variables. The aim of this study was to examine whether there were significant differences on AED adverse effects between youth with normative and subclinical/clinical depressive and/or anxiety symptoms.

Methods: As part of a larger multisite validation study, 231 youth age 5 to 18 years diagnosed with epilepsy and their caregivers were recruited to participate for the current study.

Validation of the PedsQL Epilepsy Module: A pediatric epilepsy-specific health-related quality of life measure.

Objective: To validate a brief and reliable epilepsy-specific, health-related quality of life (HRQOL) measure in children with various seizure types, treatments, and demographic characteristics.

Methods: This national validation study was conducted across five epilepsy centers in the United States. Youth 5-18 years and caregivers of youth 2-18 years diagnosed with epilepsy completed the PedsQL Epilepsy Module and additional questionnaires to establish reliability and validity of the epilepsy-specific HRQOL instrument.

Implementation of psychological clinical trials in epilepsy: Review and guide.

The International League Against Epilepsy (ILAE) Neuropsychiatry commission and United States Institute of Medicine report both identified cognitive and psychological comorbidities as a significant issue for individuals with epilepsy, with rates as high as 60%. However, there is a paucity of evidence-based treatments for many psychological conditions (e.g.

Prediction of specific depressive symptom clusters in youth with epilepsy: The NDDI-E-Y versus Neuro-QOL SF.

Objective: Proper assessment and early identification of depressive symptoms are essential to initiate treatment and minimize the risk for poor outcomes in youth with epilepsy (YWE). The current study examined the predictive utility of the Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y) and the Neuro-QOL Depression Short Form (Neuro-QOL SF) in explaining variance in overall depressive symptoms and specific symptom clusters on the gold standard Children's Depression Inventory-2 (CDI-2).

Methods: Cross-sectional study examining 99 YWE (female 68, mean age 14.

Behavioral health in young adults with epilepsy: Implications for transition of care.

Aim: Neurodevelopmental and behavioral health disorders commonly occur with epilepsy, yet risk for young adults is unknown. The aim of this study was to determine the distribution and risk characteristics of neurodevelopmental and behavior health comorbidities among young adults with epilepsy compared with those among young adults with migraine and healthy controls.

Method: A case-control study examining hospital admission, outpatient, and emergency department (ED) visits for young adults with an ICD-9-CM diagnosis of epilepsy, migraine, or lower extremity fracture (LEF) was conducted.

Behavioral health referrals in pediatric epilepsy.

The purpose of this study was to examine the feasibility of a behavioral health referral protocol and barriers to behavioral health care in a pediatric epilepsy clinic. A sample of 93 youth with epilepsy ages 10-17 and caregivers completed behavioral health and seizure severity measures during a routine epilepsy clinic visit. Key findings are that 47 (50.

Surgical Management of Pediatric Epilepsy: Decision-Making and Outcomes.

First-line treatment for epilepsy is antiepileptic drug and requires an interdisciplinary approach and enduring commitment and adherence from the patient and family for successful outcome. Despite adherence to antiepileptic drugs, refractory epilepsy occurs in approximately 30% of children with epilepsy, and surgical treatment is an important intervention to consider. Surgical management of pediatric epilepsy is highly effective in selected patients with refractory epilepsy; however, an evidence-based protocol, including best methods of presurgical imaging assessments, and neurodevelopmental and/or behavioral health assessments, is not currently available for clinicians.

Mapping the neuropsychological profile of temporal lobe epilepsy using cognitive network topology and graph theory.

Objective: Normal cognitive function is defined by harmonious interaction among multiple neuropsychological domains. Epilepsy has a disruptive effect on cognition, but how diverse cognitive abilities differentially interact with one another compared with healthy controls (HC) is unclear. This study used graph theory to analyze the community structure of cognitive networks in adults with temporal lobe epilepsy (TLE) compared with that in HC.

Intrinsic functional connectivity underlying successful emotion regulation of angry faces.

Most of our social interaction is naturally based on emotional information derived from the perception of faces of other people. Negative facial expressions of a counterpart might trigger negative emotions and initiate emotion regulatory efforts to reduce the impact of the received emotional message in a perceiver. Despite the high adaptive value of emotion regulation in social interaction, the neural underpinnings of it are largely unknown.

Development and validation of the NDDI-E-Y: a screening tool for depressive symptoms in pediatric epilepsy.

Objectives: To validate the revised 12-item revised Neurological Disorders Depression Inventory-Epilepsy for Youth (NDDI-E-Y), a self-report screening tool for depressive symptoms tailored to youth ages 12-17 with epilepsy.

Methods: Youth at two sites completed the NDDI-E-Y during a routine epilepsy visit. Youth at one site also completed the Children's Depression Inventory-2 (CDI-2).

Determining patient needs: A partnership with South Carolina Advocates for Epilepsy (SAFE).

Purpose: The purpose of this study was to collaborate with a community partner to administer a current needs assessment of persons with epilepsy (PWE) and determine the types of resources that PWE would like to access through the community partner.

Methods: A self-report needs assessment survey was administered to caregivers and PWE across the state of South Carolina during a community partner educational workshop (n=20) and via secure software distributed through an email link (n=54).

Key Findings: The most frequently reported challenges (>50%) were concerns about finding time to participate in epilepsy community activities, the personal safety of the PWE, finding social connections or social support, finding mental or behavioral health services, and work concerns.

Mapping the landscape of cognitive development in children with epilepsy.

Objective: Normal childhood development is defined by age-dependent improvement across cognitive abilities, including language, memory, psychomotor speed and executive function. Epilepsy is often associated with a global disruption in cognitive development, however, it is still largely unknown how epilepsy affects the overall organization of overlapping cognitive domains. The aim of the study was to evaluate how childhood epilepsy affects the developmental interrelationships between cognitive domains.

Translating working memory into action: behavioral and neural evidence for using motor representations in encoding visuo-spatial sequences.

The neurobiological organization of action-oriented working memory is not well understood. To elucidate the neural correlates of translating visuo-spatial stimulus sequences into delayed (memory-guided) sequential actions, we measured brain activity using functional magnetic resonance imaging while participants encoded sequences of four to seven dots appearing on fingers of a left or right schematic hand. After variable delays, sequences were to be reproduced with the corresponding fingers.

Shifted neuronal balance during stimulus-response integration in schizophrenia: an fMRI study.

Schizophrenia is characterized by marked deficits in executive and psychomotor functions, as demonstrated for goal-directed actions in the antisaccade task. Recent studies, however, suggest that this deficit represents only one manifestation of a general deficit in stimulus-response integration and volitional initiation of motor responses. We here used functional magnetic resonance imaging to investigate brain activation patterns during a manual stimulus-response compatibility task in 18 schizophrenic patients and 18 controls.

Crossmodal emotional integration in major depression.

Major depression goes along with affective and social-cognitive deficits. Most research on affective deficits in depression has, however, only focused on unimodal emotion processing, whereas in daily life, emotional perception is often highly dependent on the evaluation of multimodal inputs. We thus investigated emotional audiovisual integration in patients with depression and healthy subjects.

Task- and resting-state functional connectivity of brain regions related to affection and susceptible to concurrent cognitive demand.

A recent fMRI-study revealed neural responses for affective processing of stimuli for which overt attention irrespective of stimulus valence was required in the orbitofrontal cortex (OFC) and bilateral amygdala (AMY): activation decreased with increasing cognitive demand. To further characterize the network putatively related to this attenuation, we here characterized these regions with respect to their functional properties and connectivity patterns in task-dependent and task-independent states. All experiments of the BrainMap database activating the seed regions OFC and bilateral AMY were identified.

Modulation of affective face processing deficits in Schizophrenia by congruent emotional sounds.

Schizophrenia is a psychiatric disorder resulting in prominent impairments in social functioning. Thus, clinical research has focused on underlying deficits of emotion processing and their linkage to specific symptoms and neurobiological dysfunctions. Although there is substantial research investigating impairments in unimodal affect recognition, studies in schizophrenia exploring crossmodal emotion processing are rare.